Kidney Preservation for Transplantation

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DESCRIPTION (provided by applicant): Renal transplantation is the most effective and cost efficient treatment for patients with established renal disease. However ischemia-reperfusion injury associated with the retrieval, storage and transplantation of kidneys from cadavers is a major immune-independent factor adversely affecting early graft function and limiting long-term graft survival. We have identified Refanalin, an organic small molecule, with significant cytoprotective activity. In animal models of ischemic, obstructive and chemotoxic renal injury, Refanalin treatment prevented kidney dysfunction and reduced apoptotic and necrotic cell death. The present proposal explores the therapeutic potential of this small molecule in the setting of renal transplantation. By preventing ischemia-reperfusion related renal cell death, Refanalin can preserve both graft viability and function, prevent graft rejection and reduce recipient mortality. The studies in the current proposal are intended to provide sufficient supporting data for in-depth, pre-clinical Phase II studies examining Refanalin efficacy in large animal models of renal transplant.